Farmacocinética de propofol en potrillos de 10 a 15 días de edad

Baroni, E.; Ahumada, Fernando Valenzuela; Lüders, Carlos; Saavedra, Iván; Zambucetti, R.

doi:10.4067/s0301-732x2000000200006

Cited by 1 publication

(5 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is also in agreement with the high distribution spaces reported in all pharmacokinetic studies in several mammalian species (Servin et al 1988, Kanto and Gepts 1989, Zoran et al 1993, Baroni et al 2000. The high cellular concentrations most probably reflect binding to cellular structures, including membranes and proteins.…”

Section: Discussionsupporting

confidence: 80%

“…There are two fundamental differences between the present study and the pharmacokinetic studies carried out with several species (Servin et al 1988, Kanto and Gepts 1989, Zoran et al 1993, Baroni et al 2000. The first is rather obvious, i.e.…”

Section: Discussionmentioning

confidence: 70%

“…It is possible, though not yet demonstrated, that flow-limited distribution also occurs in other organs that can transform propofol. This would justify the assumption of most pharmacokinetic studies of a central compartment where biotransformation occurs, this central compartment being thus composed of blood, liver and eventually other propofoltransforming organs (Servin et al 1988, Kanto and Gepts 1989, Zoran et al 1993, Baroni et al 2000.…”

Section: Discussionmentioning

confidence: 99%

“…Conclusions have oscillated between the two-and three-compartment models, sometimes within the same experimental series (Kanto andGepts 1989, Zoran et al 1993). It is certainly not fortuitous that standard deviations of the fitted parameters, such as half-life times, are generally very high (Kanto and Gepts 1989, Zoran et al 1993, Baroni et al 2000. All these characteristics reveal a very complex behaviour for propofol in the whole organism, which can be only described imprecisely by the current relatively simple compartmental models.…”

Section: Introductionmentioning

confidence: 96%

“…Propofol is also known to affect energy transduction in isolated mitochondria (Branca et al 1991a, b). Consistently with the high affinity for lipophilic structures, the apparent distribution space of propofol in whole organisms is very high, generally exceeding the true physical limits (Kanto and Gepts 1989, Baroni et al 2000, Weaver et al 2001. Besides the high distribution space, the pharmacokinetics of propofol are quite complex.…”

Section: Introductionmentioning

confidence: 96%

See 4 more Smart Citations

Transport, transformation and distribution space of propofol in the rat liver studied by means of the indicator-dilution technique

Acco¹,

Bracht²

2004

Xenobiotica

View full text Add to dashboard Cite

1. The transport, transformation and distribution space of the endovenous anaesthetic propofol in the isolated perfused rat liver were investigated by using the multiple-indicator dilution technique with constant infusion (step input). 2. The behaviour of propofol in the liver was described by a space-distributed variable transit-time model. The drug permeated the cell membrane at very high rates and its distribution into the cellular space was flow-limited. The apparent distribution space of propofol varied between 284 and 125 times the water space, and was inversely related to the tested portal concentrations (33-250 microM). 3. The corresponding ratios of intra- to extracellular concentration varied between 319 and 187, revealing a very high affinity of the liver for propofol. They most probably reflect binding to several cellular structures, including membranes and proteins. 3. The single-pass rate coefficients for biotransformation decreased with increases in the portal concentration of propofol. The liver released significant amounts of 4-hydroxypropofol, reaching 41.7 % of the total single pass of 67.2 microM propofol biotransformation. These results disprove previous notions that hydroxylation is rate limiting for conjugation and suggest that the liver might function as a 4-hydroxypropofol source for conjugation to glucuronic acid or sulfate in other tissues.

show abstract

Section: Discussionsupporting

confidence: 80%